Adam Foye, 11, counts down to the day his family learns the root cause of his inherited muscle-weakening disease.

courtesy of Sarah Foye

By Carolyn Y. Johnson

Globe Staff | 11.07.12 | 1:58 PM

In the Foye household in Pine Brook, N.J., a biomedical twist on an Advent calendar went up on the fireplace mantel in early October: a countdown to the long-awaited day they would find out what gene caused 11-year-old Adam Foye’s mysterious and rare muscle-weakening disease.

Each day, a different family member—mom, dad, Adam, grandma—pulled off a numbered sticky note, ticking off the days until a mid-October conference call. That day, the family got a precious answer, learning the fruits of a contest organized by Boston Children’s Hospital. Twenty-three teams of scientists from around the world had combed through the DNA blueprints of Adam and his parents, Sarah and Patrick, to try and understand why Adam tired so easily, needing a scooter to walk longer than a few blocks and requiring a ventilator to help him breathe at night.

What they found was that Adam’s disease, called centronuclear myopathy, stemmed from mutations in a giant gene called titin.

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“It answers so many questions,” said Sarah Foye. “You have a child with this disorder, and everyday I look at him and he’s too tired to play and too tired to go to school. I always ask what is it, what is causing this, and what can I do to help.”

Identifying the gene is only a first step, but an important one. Researchers at Boston Children’s have a zebrafish with the same gene mutations that will allow them to screen for drugs that might help Adam. The finding, however, also suggests that a potential drug trial that is being developed for a similar condition would not work for Adam, knowledge that will spare him the unnecessary treatments that often come with downsides.

“We can now say that drug has virtually no chance of working, which is disappointing on one level, but is also an important result because every drug has side effects,” and Adam can be spared those, said Alan Beggs, director of the Manton Center for Orphan Disease Research at the hospital and a co-organizer of the contest.

Beyond the solace provided to the Foye family, the contest aimed to provide new thinking on how to deal with many of the problems that come with the unprecedented amount of personal information provided by DNA-sequencing technologies. As the cost of obtaining a person’s genome plummets, scientists and clinicians are wrestling with how to extract meaning from such large amounts of data, how to present it in a comprehensible way to physicians and patients, and how to best handle incidental findings that might emerge when studying the genome.

“The dilemma now is to identify the key changes, or mutations, that are responsible for the patient’s medical condition, and determine which they are against this background of enormous normal variation” in human DNA sequences, Beggs said. “The purpose of the challenge was to develop best practices for the interpetation and return of these new types of data to patients’ physicians.”

The winner of a $15,000 prize was the Division of Clinical Genetics at Brigham and Women’s Hospital. Teams were given the full genome sequences from three families. Each had a child with a rare genetic disease that stemmed from an unknown cause, and teams took on the massive challenge of pinpointing the probable cause of their muscle weakness or cardiac defects, but also addressing other issues that arise when sequencing the genome.

For example, the teams wrote up reports that could be provided to physicians that would allow them to explain the genetic mutation to each patient’s family. Some teams provided samples of the consent form they would ask a patient and family members to sign before providing their DNA to doctors, requesting, for example, whether they would want to receive incidental information—such as the risk for another kind of illness that might lie in their genes, but was not the focus of the study.

The results were presented at the meeting of the American Society of Human Genetics on Wednesday, and Beggs said that his Boston Children’s group planned to comb through the submissions by each team and write a paper about the best practices that emerged in the contest.

A cake to celebrate the discovery of the gene that underlies Adam Foye’s muscle-weakening disease.

courtesy of Sarah Foye

The Foye family has been celebrating the finding. Because the titin gene has been linked to heart problems, the finding suggests closer cardiac monitoring might be useful. But more than anything, the family is celebrating the knowledge, with a cake that Adam helped decorate. “TITIN” is spelled out in yellow frosting.